Safety and Efficacy of Radiotherapy Combined With Immunochemotherapy in Pre-treated SCLC Patients With Liver Metastases

All eligible patients will receive liver-directed radiotherapy, followed by PD-1/PD-L1 inhibitors plus chemotherapy. The systemic therapy is initiated concurrently with radiotherapy. PD-1/PD-L1 inhibitors and chemotherapeutic agents (such as Etoposide, Nab-paclitaxel, Irinotecan, or Lurbinectedin) are administered intravenously every 3 weeks according to their approved product information. The treatment regimen consists of an initial concurrent phase of radiotherapy, immunotherapy, and chemotherapy, followed by a maintenance phase with PD-1/PD-L1 inhibitors alone until disease progression or for up to 24 months.Main Objective and Endpoint:

The primary objective is to evaluate the objective response rate (ORR) and safety of the combination therapy. The primary endpoint is the ORR, defined as the proportion of subjects achieving a complete response (CR) or partial response (PR) based on RECIST v1.1 criteria, as determined by the investigator.

Inclusion criteria

• Aged 18 to 75 years, with an ECOG Performance Status of 0-2.
• Histologically confirmed stage IV non-small cell lung cancer (NSCLC) or extensive-stage small cell lung cancer, with radiologically confirmed liver metastases (at least one measurable lesion with the longest diameter ≥ 1 cm).
• Prior failure (due to progression or intolerance) to platinum-based doublet chemotherapy and PD-1/PD-L1 inhibitor therapy.
• Adequate liver function reserve (Child-Pugh class A or B, ALT/AST ≤ 5 × ULN, total bilirubin ≤ 1.5 × ULN).
• Life expectancy of at least 3 months.
• Normal function of major organs and no severe dysfunction of the hematopoietic, cardiac, pulmonary, hepatic, renal, or bone marrow systems, or immunodeficiency diseases.
• Within one week prior to enrollment, bone marrow and organ function meet the following criteria:Hemoglobin ≥ 80 g/L, neutrophil count ≥ 1.5 × 10⁹/L, and platelet count ≥ 70 × 10⁹/L. Renal function: Serum creatinine ≤ 1.5 × ULN, and endogenous creatinine clearance rate ≥ 55 ml/min.Liver function: Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN (if liver metastases are present, total bilirubin ≤ 3 × ULN and transaminases ≤ 5 × ULN are acceptable).
• Voluntarily participates and provides written informed consent.
• Good compliance and willingness to adhere to the study visit schedule and other protocol requirements.
• Willingness to provide blood and tissue samples for biomarker testing.
• Judged by the radiation oncologist to have no contraindications to liver radiotherapy. Patients who agree to receive immunotherapy, chemotherapy, and radiotherapy.
• For patients of childbearing potential: agreement to use effective contraception during the study period and for at least 6 months after the last study treatment; negative serum or urine pregnancy test within 7 days prior to study entry; and not breastfeeding. Male patients with partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose.

Exclusion criteria

• Presence of any active autoimmune disease or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism [may be included if controlled with hormone replacement therapy]); prior liver radiotherapy or liver transplantation; history of liver cirrhosis (Fibroscan ≥ F3), portal hypertension, or hepatic encephalopathy.
• Congenital or acquired immunodeficiency, such as Human Immunodeficiency Virus (HIV) infection, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive HCV antibody and HCV RNA above the lower limit of detection of the assay), or co-infection with both hepatitis B and C.
• Uncontrolled or significant cardiac disease, including: (a) NYHA Class II or higher heart failure; (b) Unstable angina; (c) Myocardial infarction within the past 1 year; (d) Patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
• Severe infection or serious comorbidities within 4 weeks prior to the first dose of study treatment.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• History of other primary malignancies within the past 5 years.
• Known allergy to any of the trial drugs or their excipients.
• Pregnant or lactating women, or subjects of childbearing potential unwilling to use effective contraception during the study period.
• Patients with Child-Pugh class B or C liver insufficiency.
• Any other contraindication as determined by the investigator to preclude participation in the study.